The ability to detect, and the innate liking for, sweet-tasting compounds presumably arose in animals to insure an adequate intake of calories and other nutrients. However, excess consumption of some sweet substances by humans has been implicated in a number of health disorders. The mechanisms by which sweeteners are detected and their intake regulated remain unclear although much progress has recently been made. In this project, primarily employing the inbred mouse as a model system, we use behavioral, physiological and molecular biological techniques to further our understanding of factors regulating sweetener perception and ingestion. Recently, we fine-mapped one genetic locus, Sac, to a small region of mouse distal chromosome 4 where we and other investigators have now identified a gene that codes for a sweet receptor. Yet a number of lines of evidence indicate that other genes that may specify additional receptors, transductive elements or central nervous system structures must be involved in determining sweet taste perception, preference and intake. During the project period, we will use a number of tools, some of them newly available, to locate and eventually identify novel genes important in regulating perception and intake of sweeteners. The results of this work will further understanding of sweetness perception, the sense of taste, and sensory biology.